There are significant potential human health effects caused by exposure to Pfiesteria piscicida or morphologically related organisms. We recently had the opportunity to systematically study a series of symptomatic individuals (n=24) who were exposed to estuary waters with documented toxic activity of this organism. Our findings indicated that disturbances in selective attention, new learning and memory were the only medical findings that consistently distinguished the exposed from non-exposed cases. Moreover, the risk for having a new learning problem increased with the intensity and duration of exposure to infected waterways. Neurologic data was consistent with a mild encephalopathic process involving primary the frontal and temporal lobes. FDG PET studies found areas of abnormal activation predominantly in the regions of the frontal and temporal lobes, cerebral regions strongly implicated in the memory process. Therefore, it is hypothesized that exposure to water containing Pfiesteria-related toxins will produce a reversible, focal encephalopathic process involving regions of the frontal and temporal lobes related to selective attention and memory process. To test this hypothesis, this investigation will (1) characterize the specificity, severity and patterns of selective attention and memory disturbances in a cohort of symptomatic cases; (2) correlate the neuropsychological findings with clinical neurologic data (neurology exam, EEG, lumbar puncture, MRI and FDG PET); (3) correlate the neuropsychological findings with metabolic and functional imaging measures (PET, fMRI) and (4) demonstrate the neuropsychological finding with metabolic and function imaging measures (PET, fMRI) and (4) demonstrate the reversibility of the neuropsychological deficits. Standardized, state- of-the-art neuroimaging and functional imaging procedures will be applied in a case-control research design. A subgroup of participants will participate in a longitudinal study. Data will be analyzed using analysis of variance and logistic regression procedures. Findings will increase knowledge about the specific neurotoxic effects of Pfiesteria exposure in humans, the individuals characteristics of persons at greater risk for exposure-related cognitive disturbances, the natural progression of the illness and the neural mechanisms which subserve the neuropsychologic alterations.